Abstract LB110: Racial and ethnic disparities associated with the intratumor microbiome in female cancers
Authors: Matthew Uzelac, Wei Tse Li, Jaideep Chakladar, Daniel John, Weg M. Ongkeko
Journal: Cancer Research (2023)

Abstract Background: The intratumor microbiome is implicated in tumor initiation, progression, and altered immune response to cancer therapies. Furthermore, recent studies have revealed correlations between microbial abundance and racial disparities in cancer. While these investigations provide novel insights into cancer disparities research, few have investigated which racial and ethnic disparities exist for patients with female malignancies. In this study, we characterized the intratumor microbiome according to racial and ethnic disparities in common female malignancies including breast, cervical, uterine, and ovarian cancers. Methods: We examined the intra-tumoral microbiome in the breasts, cervix, uterus, and ovaries (n = 2630). Raw tumor RNA sequencing data were downloaded from The Cancer Genome Atlas (TCGA) and aligned to bacterial genomes using the PathoScope 2.0 framework and references genomes provided by the NCBI nucleotide database. Potential contaminants were identified and removed from downstream analyses by associating individual microbe abundance with total microbe abundance in each sample. Microbial abundance was correlated to race, ethnicity, and prognostic variables (Kruskal-Wallis test or Cox regression, p &amp;lt; 0.05). Finally, we validated our results using transcriptomic sequencing data downloaded from the GEO NCBI data portal. Results: Significant dysregulation of bacterial microbes according to race and ethnicity was observed in these cancers, but most notably in breast cancer in which 6 species correlated strongly with survival. Of particular significance were Veillonella Parvula and Mycobacteroides chelonae, which were both significantly dysregulated in Black breast cancer patients, with low abundance of both species correlating to poor survival. Cupriavidus Taiwanensis and Delftia Acidovorans were more abundant in Black breast cancer patients, with high abundance correlating to poorer prognosis. Black patients were also diagnosed at significantly later cancer stages in cervical cancer. We also observed significant correlations of bacterial microbe abundance with prognostic and treatment variables in these cancers, including pathologic TNM staging, neoplasm presence, therapy outcome, and more. Conclusion: Our study is the most comprehensive to date investigating racial differences in the intra-tumoral microbiome in common female cancers. We found that differences in intratumoral microbial abundance may account in part for observed racial and ethnic disparities in cancer prevalence and progression in these cancers. Further studies are needed to investigate the specific mechanisms by which these microbes contribute to these observed cancer disparities within the tumor microenvironment. Citation Format: Matthew Uzelac, Wei Tse Li, Jaideep Chakladar, Daniel John, Weg M. Ongkeko. Racial and ethnic disparities associated with the intratumor microbiome in female cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB110.